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RECQL deficiencies

Tuesday 28 October 2003

Defects in any of three RecQ family members (BLM, WRN or RECQ4) give rise to cancer predisposition disorders. These are Bloom syndrome, Werner syndrome and Rothmund-Thomson syndrome. Bloom syndrome is uniquely associated with a predisposition to cancers of all types.

Deficiency in a helicase of the RecQ family is found in at least three human genetic disorders associated with cancer predisposition and/or premature ageing. The RecQ helicases encoded by the BLM, WRN and RECQ4 genes are defective in Bloom’s, Werner’s and Rothmund-Thomson syndromes, respectively.

Cells derived from individuals with these disorders in each case show inherent genomic instability. Recent studies have demonstrated direct interactions between these RecQ helicases and human nuclear proteins required for several aspects of chromosome maintenance, including p53, BRCA1, topoisomerase III, replication protein A and DNA polymerase.

Recent data indicate that mutations in genes encoding helicases are responsible for genomic instability disorders of man.

The functional importance of RecQ family helicases in the maintenance of genome integrity is highlighted by the identification of five human RecQ family helicases, three of which are involved in autosomal recessive genomic instability disorders associated with cancer predisposition and/or premature ageing.

These disorders, which are discussed in detail below are Bloom syndrome (BS), Werner syndrome (WS) and Rothmund-Thomson syndrome (RTS).


- RECQL1: no disorder associated
- RECQL2 (MIM.604611): mutations in the Werner syndrome (WRN) (MIM.277700)
- RECQL3 (MIM.604610) (15q26.1): mutations in the Bloom syndrome (BLM) (MIM.210900)
- RECQL4 (MIM.603781) : mutations in the Rothmund-Thomson syndrome (MIM.268400) and RAPADILINO syndrome
- RECQL5 (MIM.603781): no disorder associated


- Mohaghegh, P.; Hickson, I. D. DNA helicase deficiencies associated with cancer predisposition and premature ageing disorders. Hum. Molec. Genet. 10: 741-746, 2001. PubMed ID : 11257107

- Shen JC, Loeb LA. The Werner syndrome gene: the molecular basis of RecQ helicase-deficiency diseases. Trends Genet. 2000 May;16(5):213-20. PMID: 10782115